We propose a program to integrate biomedical (Rush Medical College) with bioengineering (Illinois Institute of Technology and Massachusetts Institute of Technology) approaches to test and refine a novel X-ray technology for the diagnosis of joint pathology, particularly osteoarthritis. This technology may aid in the development of disease modifying agents and treatment strategies for the prevention and treatment of joint diseases. This project utilizes a novel synchrotron x-ray technique called diffraction enhanced imaging (DEI) which derives dramatic gains in contrast over conventional radiographs by exploiting x-ray refraction and scatter rejection (extinction) in addition to the usual absorption of conventional radiography. This technique, originally developed for mammary carcinoma imaging analyzes soft tissue as high contrast images with very high (greater than 0.05mm) spatial resolution. Although the synchrotron is currently used for DE imaging, the technique is not, in principle, tied to it. We have already shown that DEI is capable of imaging normal and degenerated articular cartilage of synovial joints showing features unique to this type of imaging using exposure times comparable to those of ordinary radiography. Beginning in the first year, we will interpret the cartilage and bone data obtained through our DEI methodologies by using the biological profiles of the matrix components as garnered through morphologic, biochemical and biophysical analysis. Some of the features observed in the DE images are not immediately explainable in molecular, chemical or structural terms. By using a unique integrated experimental approach, correlating biochemical and morphological tissue profiles with DE images, we hope to refine the overall DEI system for the detection of joint disease and, potentially, for other pathologies. We will image human and animal synovial joints and begin the refinement of the imaging technique for the optimal identification of early cartilage lesions. Animal models of cartilage degeneration will be used particularly for DE imaging of cartilage prior to visible signs of degeneration. Beginning in year two, we will image human cartilage that has been biomechanically damaged under controlled conditions for observation through DE imaging. We will also begin developing new DEI methodologies to produce images conveying more comprehensive information about the properties of the cartilage tissue, first for planar and then for 3D computed tomography. Throughout years one through five of the proposed project, there will be an iterative process of comparing biological analytical data with imaging data for the refinement of the DEI technique for joint tissues. Our long-term goal is to identify and localize initial phases of cartilage degeneration and follow their progression with the ultimate aim of monitoring disease progression and therapeutic interventions.